Bench-to-bedside review: Sepsis is a disease of the microcirculation

Microcirculatory perfusion is disturbed in sepsis. Recent research has shown that maintaining systemic blood pressure is associated with inadequate perfusion of the microcirculation in sepsis. Microcirculatory perfusion is regulated by an intricate interplay of many neuroendocrine and paracrine pathways, which makes blood flow though this microvascular network a heterogeneous process. Owing to an increased microcirculatory resistance, a maldistribution of blood flow occurs with a decreased systemic vascular resistance due to shunting phenomena. Therapy in shock is aimed at the optimization of cardiac function, arterial hemoglobin saturation and tissue perfusion. This will mean the correction of hypovolemia and the restoration of an evenly distributed microcirculatory flow and adequate oxygen transport. A practical clinical score for the definition of shock is proposed and a novel technique for bedside visualization of the capillary network is discussed, including its possible implications for the treatment of septic shock patients with vasodilators to open the microcirculation.

[1]  K. Vollebregt,et al.  Comparison of OPS imaging and conventional capillary microscopy to study the human microcirculation. , 2001, Journal of applied physiology.

[2]  R. Bone,et al.  The pathogenesis of sepsis. , 1991, Annals of internal medicine.

[3]  K. Messmer,et al.  Orthogonal polarization spectral imaging: A new method for study of the microcirculation , 1999, Nature Medicine.

[4]  J. Vincent,et al.  Red blood cell rheology in sepsis , 2003, Intensive Care Medicine.

[5]  M. Nalos,et al.  Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia , 2003, Intensive Care Medicine.

[6]  William Harvey,et al.  Exercitatio anatomica de motu cordis et sanguinis in animalibus : Frankfurt, 1628 , 1998 .

[7]  C. Ince,et al.  Opening the microcirculation: can vasodilators be useful in sepsis? , 2002, Intensive Care Medicine.

[8]  J. Hassett,et al.  Vasodilator therapy in clinical sepsis with low output syndrome. , 1978, The Journal of surgical research.

[9]  M. Fink.  Cytopathic hypoxia in sepsis , 1997, Acta anaesthesiologica Scandinavica. Supplementum.

[10]  S. Cain,et al.  Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation. , 1995, Journal of applied physiology.

[11]  M. Bristow,et al.  Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol. , 2001, International journal of cardiology.

[12]  Christoph Abels,et al.  Characterization and prevention of phototoxic effects in intravital fluorescence microscopy in the hamster dorsal skinfold model , 2000, Langenbeck's Archives of Surgery.

[13]  L. Kaplan,et al.  Start with a subjective assessment of skin temperature to identify hypoperfusion in intensive care unit patients. , 2001, The Journal of trauma.

[14]  S. Torres,et al.  Histochemical and ultrastructural study of skeletal muscle in patients with sepsis and multiple organ failure syndrome (MOFS). , 1998, Histology and histopathology.

[15]  Robin Ed.  Of men and mitochondria: coping with hypoxic dysoxia. The 1980 J. Burns Amberson Lecture. , 1980 .

[16]  J. Bakker,et al.  Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: Effect on survival in patients with septic shock* , 2004, Critical care medicine.

[17]  P. Schumacker,et al.  Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia. , 1988, Journal of applied physiology.

[18]  A. S. Relman.  Lactic acidosis. , 1971, Transactions of the American Clinical and Climatological Association.

[19]  J Tinker,et al.  The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients. , 1987, The New England journal of medicine.

[20]  D. Bredle.  Elevation of cardiac output and oxygen delivery improves outcome in septic shock. , 1993, Chest.

[21]  Michael D Sharpe,et al.  Bench-to-bedside review: Microvascular dysfunction in sepsis –hemodynamics, oxygen transport, and nitric oxide , 2003, Critical care.

[22]  Cronenwett Jl,et al.  Direct measurement of arteriovenous anastomotic blood flow in the septic canine hindlimb. , 1979 .

[23]  C. Ince,et al.  The Rationale for Vasodilator Therapy in Sepsis , 2002 .

[24]  P. Pelosi,et al.  A Trial of Goal-Oriented Hemodynamic Therapy in Critically Ill Patients , 1995 .

[25]  H. Lehr,et al.  Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy? , 2000, The Journal of pathology.

[26]  J. Vincent,et al.  Effects of nitric oxide on blood flow distribution and O2 extraction capabilities during endotoxic shock. , 1997, Journal of applied physiology.

[27]  Shuiping Zhao,et al.  The changes of circulating tumor necrosis factor levels in patients with congestive heart failure influenced by therapy. , 1999, International journal of cardiology.

[28]  C. Hinds,et al.  Response of critically ill patients to treatment aimed at achieving supranormal oxygen delivery and consumption. Relationship to outcome. , 1993, Chest.

[29]  H J Meiselman,et al.  Red blood cell aggregation in experimental sepsis. , 1997, The Journal of laboratory and clinical medicine.

[30]  C. Ince,et al.  Microcirculatory oxygenation and shunting in sepsis and shock. , 1999, Critical care medicine.

[31]  John Land,et al.  Association between mitochondrial dysfunction and severity and outcome of septic shock , 2002, The Lancet.

[32]  Craig Petersen.  D-lactic acidosis. , 2005, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[33]  P. Pelosi,et al.  A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. , 1996, The New England journal of medicine.

[34]  S. Cain,et al.  Experimental models of pathologic oxygen supply dependency , 1991, Critical care medicine.

[35]  C. Ince,et al.  Low-volume resuscitation with a hemoglobin-based oxygen carrier after hemorrhage improves gut microvascular oxygenation in swine. , 1998, The Journal of laboratory and clinical medicine.

[36]  W. Harvey.  Classic pages in obstetrics and gynecology. Exercitatio anatomica de motu cordis et sanguinis in animalibus. , 1929, American journal of obstetrics and gynecology.

[37]  H. Bruining,et al.  Nitric oxide causes dysfunction of coronary autoregulation in endotoxemic rats. , 1997, Cardiovascular research.

[38]  E. Robin.  Of men and mitochondria: coping with hypoxic dysoxia. The 1980 J. Burns Amberson Lecture. , 2015, The American review of respiratory disease.

[39]  J. Vincent.  Hemodynamic support in septic shock , 2001, Intensive Care Medicine.

[40]  H. Lehr,et al.  Intravital Fluorescence Microscopy: Impact of Light-induced Phototoxicity on Adhesion of Fluorescently Labeled Leukocytes , 1997, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[41]  P. Marik,et al.  Sublingual capnometry versus traditional markers of tissue oxygenation in critically ill patients* , 2003, Critical care medicine.

[42]  J. Vincent,et al.  Effect of vasopressin on sublingual microcirculation in a patient with distributive shock , 2003, Intensive Care Medicine.

[43]  W. Sibbald,et al.  Microvascular perfusion is impaired in a rat model of normotensive sepsis. , 1994, The Journal of clinical investigation.

[44]  Microcirculatory weak units--an alternative explanation. , 2000, Critical care medicine.

[45]  J. Vincent,et al.  A dobutamine test can disclose hepatosplanchnic hypoperfusion in septic patients. , 1999, American journal of respiratory and critical care medicine.

[46]  J. Cronenwett,et al.  Direct measurement of arteriovenous anastomotic blood flow in the septic canine hindlimb. , 1979, Surgery.

[47]  P. Vallance.  Exploring Vascular Nitric Oxide in Health and Disease , 1997, Journal of the Royal College of Physicians of London.

[48]  C. Lush,et al.  Microvascular Dysfunction in Sepsis , 2000, Microcirculation.

[49]  H. Becker,et al.  The effects of prostacyclin on gastric intramucosal pH in patients with septic shock , 1995, Intensive Care Medicine.

[50]  Florian Lang,et al.  Passive Deformability of Mature, Immature, and Active Neutrophils in Healthy and Septicemic Neonates , 1998, Pediatric Research.

[51]  J. Vincent,et al.  Effects of nitric oxide in septic shock. , 2000, American journal of respiratory and critical care medicine.

[52]  William Harvey.  Exercitatio Anatomica do Motu Cordis et Sanguinis in Animalibus , 1929, Nature.

[53]  A. Groeneveld,et al.  Circulating endothelin and nitrate-nitrite relate to hemodynamic and metabolic variables in human septic shock. , 1999, Shock.

[54]  Jean-Charles Preiser,et al.  Microvascular blood flow is altered in patients with sepsis. , 2002, American journal of respiratory and critical care medicine.

[55]  M. Pavesi,et al.  Impact of oligon central venous catheters on catheter colonization and catheter-related bloodstream infection , 2003, Critical care medicine.

[56]  M. Haumer,et al.  Milrinone therapy in catecholamine‐dependent critically ill patients with heart failure , 2000, Acta anaesthesiologica Scandinavica.

[57]  Z. Ba,et al.  Endothelium-dependent relaxation is depressed at the macro- and microcirculatory levels during sepsis. , 1995, The American journal of physiology.

[58]  E. Rackow,et al.  Microvascular function and rheologic changes in hyperdynamic sepsis. , 1995, Critical care medicine.

[59]  C. Hinds,et al.  Elevation of systemic oxygen delivery in the treatment of critically ill patients. , 1994, The New England journal of medicine.

[60]  J. Vincent,et al.  Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. , 1991, Chest.

[61]  S. Carley,et al.  Trauma education. , 2001, Resuscitation.

[62]  E. Erdmann.  The effect of positive inotropes on the failing human myocardium. , 1997, Cardiology.

[63]  S. Baker,et al.  Predictive value of the stomach wall pH for complications after cardiac operations: comparison with other monitoring. , 1987, Critical care medicine.

[64]  C. Ince,et al.  Microvascular oxygen pressure in the pig intestine during haemorrhagic shock and resuscitation , 1999, The Journal of physiology.

[65]  C. Lavie,et al.  The clinical relevance of circulating tumor necrosis factor-alpha in acute decompensated chronic heart failure without cachexia. , 1996, Chest.

[66]  U. Förstermann,et al.  Nitric oxide in the pathogenesis of vascular disease , 2000, The Journal of pathology.

[67]  J. Vincent,et al.  Yearbook of Intensive Care and Emergency Medicine , 1995, Yearbook of Intensive Care and Emergency Medicine.

[68]  B. Zweifach,et al.  Microvascular adjustments during irreversible hemorrhagic shock in rat skeletal muscle. , 1985, Microvascular research.

[69]  P. Marik.  Sublingual capnography: a clinical validation study. , 2001, Chest.

[70]  Initial Clinical Experience with OPS Imaging for Observation of the Human Microcirculation , 2001 .

[71]  Can Ince,et al.  Nitroglycerin in septic shock after intravascular volume resuscitation , 2002, The Lancet.

[72]  E. Ivers,et al.  Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock , 2001 .